The spread of AIDS through heterosexual contact has been dramatic in Africa. In Rwanda, a small central African country, the prevalence of infection in urban adults now exceeds 30%. Our cohort studies have shown that one couples in seven in the capital city have discordant HIV serology results, and that the transmission rate in this group after HIV testing and counseling is 7% per year. The study of discordant couples offers the best opportunity to identity the determinants of heterosexual transmission in both HIV and positive index case and in the HIV negative exposed individual, and allows for comparison of female to male and male to female transmission. The mortality rate among HIV infected urban Rwandan women is 4% per year and HIV disease now accounts for 90% of deaths in this group. The most common HIV associated infectious disease is tuberculosis, and the 2 year incidence of tuberculosis in HIV positive women is over 20 times that in HIV negative controls. Using the diagnostic algorithms that are currently the standard of care, the delay between onset of symptoms and diagnosis of tuberculosis is 10-11 months. We have 5 years of experience with cohort studies in Rwanda, full support from the Rwanda government, a staff of well trained personnel, advanced laboratory capability, and an established reputation with the community. The followup rate at 3 years later is over 90% for our existing cohort studies, and we are able to recruit large numbers of new discordant couples. We propose to continue and build on our new existing studies in three major areas: 1. Expansion of our studies of heterosexual transmission of HIV through recruitment of over 600 discordant couples. 2. Continuation of our studies of the natural history of HIV infection and identification of clinical and laboratory parameters with prognostic significance. 3. Development and evaluation of an algorithm to allow the earliest possible diagnosis and treatment of tuberculosis among HIV infected adults.